This application seeks a renewal of NIA T32 AG00258 entitled Neurobehavior, Neuroendocrinology, and Genetics of AD. By the end of our second funding cycle our program will have supported 27 post-doctoral trainees (12 with M.D. degrees, 3 of whom also have PhDs, and 15 with Ph.D. degrees). Our training efforts have been successful, as evidenced by the accomplishments of our trainees, as well as by our ability to attract qualified candidates and physician trainees to our program. In the next funding cycle, we will continue to provide post-doctoral training in clinical research regarding the neurobehavior, neuroendocrinology, and neurogenetics of Alzheimer's disease (AD) and related dementias. In particular, the program will focus on training clinical researchers capable of translating critical findings from basic science into hypotheses regarding the etiology, pathophysiology, and treatment of AD. Furthermore, clinical researchers will receive specialized training in two areas of study, neuroendocrinology and neurogenetics, that hold promise for increasing our understanding of the pathogenesis of AD and for developing new therapeutic approaches. These areas are not typically emphasized in graduate training of psychiatrists, neurologists, or neuropsychologists. However, recent advances have underscored the importance of genetic factors such as amyloid precursor protein and presenilin mutations, and apolipoprotein e genotype. Neuroendocrine factors such as disruptions of lipid, insulin and glucose metabolism, inflammation, and glucocorticoid status may also play an important pathogeneticjole in modifying the effects of AD susceptibility genes, thereby affecting the neuropsychologic expression of AD. Clinical investigators capable of bridging the fields of neurogenetics, neuropsychology, and neuroendocrinology will be needed to disentangle and define these potentially critical interactions. The program is supported by the rich and interactive research environment of the University of Washington and Veterans Affairs Puget Sound Health Care System, where a critical mass of faculty conduct both basic science and clinical research in the neuroendocrinology and neurogenetics of AD. The ADRC at the UWwill also serve as a resource for faculty and trainees. Although there is a long-standing commitment to aging training at our institution, our proposed program is unique in its interdisciplinary nature and focus on clinical translational research in AD and related conditions. As such, it will provide a much-needed approach to the training of clinical research scientists whose work will address these complex disorders. RELEVANCE: Our program trains researchers who are able to translate findings from basic science into clinical models of Alzheimer's disease and other dementias, and thereby facilitate the development of new treatments for these challenging diseases. In particular, the program focuses on the interactive role played by genetic and metabolic factors such as diabetes and stress in increasing the risk of dementia. These factors are highly prevalent in our society, and a better understanding of their role may lead to new treatments and strategies for preventing dementia or delaying its onset.